E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
post-menopausal osteoporosis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10031285 |
E.1.2 | Term | Osteoporosis postmenopausal |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
(1) Objective: To assess the effect of treatment with MK-0822 50 mg once weekly on the risk of morphometrically assessed vertebral fractures compared to placebo. (2) Objective: To assess the effect of treatment with MK-0822 on the risk of hip fractures compared to placebo. (3) Objective: To assess the effect of treatment with MK-0822 on the risk of clinical non-vertebral fractures compared to placebo. (Note: for the purposes of this study, non-vertebral fractures are defined as fractures of the hip, pelvis, wrist, humerus, clavicle, leg and rib). |
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E.2.2 | Secondary objectives of the trial |
(1) Objective: To assess the effect of treatment with MK-0822 50 mg once weekly on the risk of clinical vertebral fractures compared to placebo. (2) Objective: To assess the effect of treatment with MK-0822 50 mg once weekly on height compared to placebo. (3) Objective: To assess the effect of treatment with MK-0822 50 mg once weekly on the lumbar spine, total hip, femoral neck, trochanter and distal forearm BMD compared to placebo. (4) Objective: To assess the safety and tolerability of treatment with MK-0822 50 mg once weekly compared to placebo. (5) Objective: To assess the effect of treatment with MK-0822 50 mg once weekly on biochemical indices of bone resorption (serum C-Telopeptides of Type 1 collagen [s-CTX] and urine N-Telopeptides of Type 1 collagen [u-NTX]) compared to placebo. (6) Objective: To assess the effect of treatment with MK-0822 50 mg once weekly on biochemical indices of bone formation |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient is a woman and is ≥ 65 years of age on the day of signing informed consent. 2. Patient meets one of the following: a) Patient is a candidate for osteoporosis therapy (bisphosphonates, strontium, or PTH), has BMD T-score ≤-1.5 at either the total hip or femoral neck site, BMD T-score ≥-4.0 at both sites, and has one prior vertebral fracture (defined as anterior, mid or posterior height loss of >20%). OR- b) Patient is a candidate for osteoporosis therapy (bisphosphonates, strontium, or PTH), has BMD T-score ≤-2.5 at either the total hip or femoral neck site, BMD T-score ≥-4.0 at both sites, and does not have a prior vertebral fracture (defined as anterior, mid or posterior height loss of >20%). OR - c) Patient is not a suitable candidate for, or has declined osteoporosis therapy (bisphosphonates, strontium, or PTH), has BMD T-score ≤-1.5 at either the total hip or femoral neck site, and has at least one prior vertebral fracture (defined as anterior, mid or posterior height loss of >20%). OR- d) Patient is not a suitable candidate for, or has declined osteoporosis therapy (bisphosphonates, strontium, or PTH), and has a BMD T-score ≤-2.5 at either the total hip or femoral neck site. Note: Eligibility for this criterion is based on absolute BMD in g/cm2 . 3. The patient has at least one hip that is evaluable by DXA (e.g., contains no hardware from orthopedic procedures). 4. Patient has been postmenopausal for at least 5 years, defined as no menses for at least 5 years OR at least 5 years status post bilateral oophorectomy. 5. Patient understands the study procedures, alternative treatments available and risks involved with the study, and voluntarily agrees to participate by giving written informed consent. 6. Patient is ambulatory. 7. Patient is able to read, understand, and complete questionnaires and diaries. |
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E.4 | Principal exclusion criteria |
1) Patient has chosen treatment with oral bisphosphonates or other agents demonstrated to reduce the risk of hip fracture. 2) Patient has had a prior hip fracture. 3) Patient experienced a clinical fragility fracture (including a clinical vertebral fracture) within 24 months. (Note: Finger, toe, and skull fractures should not be considered with regard to this exclusion criterion.) 4) Patient has had more than 1 prior vertebral fracture, as defined in Inclusion Criterion 1 above, and she is a suitable candidate for osteoporosis therapy (i.e., bisphosphonates, strontium, or PTH). 5) Patient has or has had evidence of a metabolic bone disorder other than osteoporosis. 6) Patient has a history of renal stones and serum calcium, serum 25-hydroxyvitamin D and serum PTH are not within normal limits. 7) Patient has active parathyroid disease. (Note: Serum PTH level should be assessed at screening for patients with a documented history of parathyroid disease. Patients with a history of primary hyperparathyroidism and with curative parathyroidectomy >2 years prior to screening are not excluded.) 8) Patient has a history of thyroid disease not adequately controlled by medication. (Note: In patients with a documented history of thyroid disease, TSH and free thyroxine index should be assessed at screening). 9) Patient has serum-creatinine >1.6 mg/dL and is considered to have severe renal insufficiency defined as calculated* creatinine clearance ≤29 ml/min (National Kidney Foundation K/DOQI Guidelines) *Calculated creatinine clearance will be done using the Cockroft and Gault method for creatinine clearance: * 0.85 with Cs = serum creatinine, and result reported in mL/min. (Note: Patients with moderate renal insufficiency (creatinine clearance 30 59 mL/min) according to NKF K/DOQI Guidelines may be included provided that serum PTH, serum hydroxy-vitamin D, serum calcium and serum phosphorus are all within normal limits.) 10) Patient has received treatment with an agent that has an effect on bone including: a) estrogen with or without progestin within the prior 6 months (Note: vaginal estrogen creams used not more than 2 times per week are allowed) b) raloxifene or other SERM (including tamoxifen), tibolone, or an aromatase inhibitor within the prior 6 months c) sub-cutaneous calcitonin within the prior 6 months (Note: use of intranasal calcitonin either prior to or during the study is permitted) d) any anabolic steroid use at any time e) systemic glucocorticoids (≥5 mg/day of prednisone or equivalent) for more than 2 weeks in the prior 6 months f) bisphosphonates: oral use more than 3 months within the prior 2 years or more than 6 months total; any lifetime use of IV zoledronate (Note: one dose of IV pamidronate or I.V. ibandronate more than 1 year prior to screening is allowed.) g) cyclosporin for more than 2 weeks within the prior 6 months |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 4 |